Large-scale comparative sequencing of primate genomes promises to reconstruct the evolutionary history of the human genome and to highlight the functional genetic differences between human and non-human primates. Regions enriched for segmental duplication are not adequately resolved within preliminary working draft genome assemblies;however, these regions contribute significantly to disease, the emergence of novel genes and are a source of considerable genetic differences between and within primate species. The object of this four-year proposal is to a) identify and validate regions of segmental duplication and structural variation in five non-human primate species (chimpanzee, orangutan, gibbon, macaque and marmoset), b) to target large-insert clones for sequencing in order to provide high-quality sequence continuity across these genetically complex regions and c) to assess the extent of polymorphism within respective populations of each primate group. The data will significantly enhance the quality of forthcoming primate genome assemblies, improve our understanding of the frequency of de novo duplications events;provide insight into the mechanisms underlying segmental duplication and improve annotation of lineage-specific gene families that lack clear orthologues within outgroup species. Such targeted studies are essential to complete our understanding of the evolution of the human genome.